Fancher provided voiceover commentary for The Criterion Collection edition DVD extras of the film noir adaptations of Ernest Hemingway's short story "The Killers", which included the 1946, 1956 and 1964 versions.

In 1959, Fancher appeared in the episode "Misfits" of the ABC western television series, The Rebel. In the storyline, Fancher used the name "Bull" with Malcolm Cassell as Billy the Kid and Hal Stalmaster as "Skinny" plot to rob a bank so that they can live thereafter without working. The "Misfits" enlist the help of The Rebel (Nick Adams) in carrying out their doomed scheme.

Fancher appeared in two Troy Donahue films: 1961's Parrish and 1962's Rome Adventure and was cast as Larry Wilson in the 1963 episode "Little Richard" of the CBS anthology series, GE True, hosted by Jack Webb. In 1965, he played the role of Hamp Fisher (a name very similar to his own), in the Perry Mason episode "The Case of the Silent Six." All in all, Fancher played roles in over fifty movies and television shows. During this time, he also had relationships with a variety of women, including Barbara Hershey and Teri Garr. Although he showed interest in screenwriting, it would take until 1977 for Fancher to transition fully into screenwriting. He continues to act occasionally.

Fancher was born to a Mexican-Danish mother and an American father, a physician, in East Los Angeles, California. At 15, he ran away to Spain to become a flamenco Dancer and renamed himself "Mario Montejo". Following the breakup of his marriage to Joann McNabb, he was married to Sue Lyon of Lolita fame from 1963 to 1965.

After trying to option Philip K. Dick's 1968 science fiction novel Do Androids Dream of Electric Sheep? in 1975, when the rights were not available, Fancher sent his friend Brian Kelly, a prospective film Producer. Dick agreed, and Fancher was brought on to write a screenplay before Kelly enlisted the support of Producer Michael Deeley. This made Fancher the executive Producer, which led to disagreements with the eventual Director Ridley Scott who then brought in David Peoples to continue reworking the script. Scott and Fancher had already clashed concerning the movie, as Scott felt the original script did not sufficiently explore the world of the movie, choosing instead to focus on the interior drama. Fancher's rewriting process was too slow for the production crew, which nicknamed him "Happen Faster".The movie was ultimately filmed and released as Blade Runner (1982).

In the early 1980s, Fancher wrote and lived outside of Los Angeles in Topanga Canyon. Fancher appeared in a cameo role in the independent film Tonight at Noon (2009), directed by Michael Almereyda and starring Rutger Hauer.

Fancher wrote two films following Blade Runner. The Mighty Quinn (1989), starred Denzel Washington, and The Minus Man (1999), starred Owen Wilson. The latter he also directed. More recently, he wrote the story and co-wrote, with Michael Green, a screenplay for Blade Runner 2049 (2017), a sequel to the 1982 film.